Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany; Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany.
Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany.
Clin Biochem. 2024 Jan;123:110703. doi: 10.1016/j.clinbiochem.2023.110703. Epub 2023 Dec 12.
Chronic kidney disease (CKD) affects over 0.5 billion people worldwide across their lifetimes. Despite a growingly ageing world population, an increase in all-age prevalence of kidney disease persists. Adult-onset forms of kidney disease often result from lifestyle-modifiable metabolic illnesses such as type 2 diabetes. Pediatric and adolescent forms of renal disease are primarily caused by morphological abnormalities of the kidney, as well as immunological, infectious and inherited metabolic disorders. Alterations in energy metabolism are observed in CKD of varying causes, albeit the molecular mechanisms underlying pathology are unclear. A systematic indexing of metabolites identified in plasma and urine of patients with kidney disease alongside disease enrichment analysis uncovered inborn errors of metabolism as a framework that links features of adult and pediatric kidney disease. The relationship of genetics and metabolism in kidney disease could be classified into three distinct landscapes: (i) Normal genotypes that develop renal damage because of lifestyle and / or comorbidities; (ii) Heterozygous genetic variants and polymorphisms that result in unique metabotypes that may predispose to the development of kidney disease via synergistic heterozygosity, and (iii) Homozygous genetic variants that cause renal impairment by perturbing metabolism, as found in children with monogenic inborn errors of metabolism. Interest in the identification of early biomarkers of onset and progression of CKD has grown steadily in the last years, though it has not translated into clinical routine yet. This systematic review indexes findings of differential concentration of metabolites and energy pathway dysregulation in kidney disease and appraises their potential use as biomarkers.
慢性肾脏病（CKD）在全球范围内影响着超过 5 亿人的生命。尽管世界人口老龄化趋势日益加剧，但各种年龄段的肾脏病患病率仍在持续上升。成人发病的肾脏病通常是由 2 型糖尿病等生活方式可改变的代谢性疾病引起的。儿科和青少年肾脏病主要由肾脏形态异常以及免疫、感染和遗传性代谢紊乱引起。尽管 CKD 的病因不同，但观察到能量代谢的改变，而其病理的分子机制尚不清楚。通过对患有肾脏病的患者的血浆和尿液中的代谢物进行系统索引，并结合疾病富集分析，发现了代谢性疾病的先天缺陷作为一个框架，将成人和儿科肾脏病的特征联系起来。肾脏病中的遗传和代谢之间的关系可以分为三个不同的领域：（i）由于生活方式和/或合并症而导致肾脏损伤的正常基因型；（ii）导致独特代谢型的杂合遗传变异和多态性，这些代谢型可能通过协同杂合性而导致肾脏病的发展；（iii）导致代谢紊乱从而导致肾脏损害的纯合遗传变异，这种情况在患有单基因代谢性疾病的儿童中发现。近年来，人们对发现 CKD 发病和进展的早期生物标志物的兴趣稳步增长，但尚未转化为临床常规。本系统评价索引了肾脏病中代谢物浓度差异和能量途径失调的发现，并评估了它们作为生物标志物的潜在用途。
